Ethyl 4-piperidinecarboxylate → Ethyl 1-(2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethyl)piperidine-4-carboxylate

Participants

Reaction Steps

To a solution of 0.355 ml of 2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethanone in 12 ml of dichloromethane were added 0.32 ml of ethyl isonipecotate, 0.58 ml of triethylamine and 1.05 ml of a toluene solution containing 1 M titanium(IV) chloride at room temperature, followed by stirring the reaction mixture at room temperature overnight. To the reaction mixture was added a solution of 392 mg of sodium cyanoborohydride in 5 ml of methanol at room temperature, followed by stirring the reaction mixture at room temperature for 6 hours. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added to the reaction mixture. An insoluble matter was filtered off using Celite. The ethyl acetate layer was separated, washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: hexane to hexane/ethyl acetate=4/1) to give the title compound as a yellow oil.

Provenance & Evidence